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Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics (IM2PACT) Into The Brain

Descrizione del progetto

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La barriera emato-encefalica e la distribuzione dei biofarmaci al cervello

L’obiettivo generale del progetto IM2PACT, finanziato dall’UE, è quello di approfondire la nostra comprensione in merito alla barriera emato-encefalica in condizioni di salute e di malattia al fine di sviluppare sistemi innovativi per la distribuzione dei biofarmaci al cervello e di individuare nuovi bersagli farmacologici per il morbo di Alzheimer, la sclerosi multipla e la malattia metabolica. I ricercatori individueranno geni specifici che abbiano subito alterazioni in seguito a malattia nelle cellule endoteliali cerebrali e, dopo aver generato e caratterizzato modelli predittivi solidi per la barriera emato-encefalica derivati da cellule staminali, stabiliranno nuovi modelli genetici di malattia. Successivamente, il loro obiettivo sarà quello di sviluppare un meccanismo efficace e sicuro e tecnologie per la distribuzione al cervello avvalendosi di sistemi di penetrazione selettiva della barriera emato-encefalica mediati da virus neurotropico, istituendo modelli in silico per prevedere la penetrazione di questa barriera a livello di terapie e farmacocinetica in diversi compartimenti del sistema neurale.

Obiettivo

The overall aim is to further the understanding of the BBB in health and disease states towards the development of innovative brain delivery systems, especially for biopharmaceuticals (e.g. peptides, antibodies, etc.) and the identification of novel disease drug targets (Alzheimer’s Disease, MS, metabolic disease). The related key deliverables will be as follows:

1.Identification and validation of specific genes and/or mechanisms which are altered in brain endothelial cells in disease.
2. Generation, validation and characterisation of robust and predictive iPSC-derived BBB models: The developed models should be more reflective of the in vivo situation than existing models, in the healthy and disease states.
3. New, efficacious and safe mechanisms and technologies of brain delivery: The output of this topic should also result in an expanded and deepened understanding of the fundamental processes that underpin drug-trafficking across the BBB, which in turn can further support endeavours to elucidate novel and more efficacious brain delivery mechanisms.
4. Characterised new genetic models for the diseases of interest in this topic which are better amenable to evaluate disease-modifying agents.
5. Characterised mechanisms of neurotropic virus-mediated BBB and CNS penetration for development of selective brain delivery systems.
6. Established in silico/mathematical models in predicting BBB penetration of therapeutics (such as receptor-or carrier-mediated transcytosis for delivery across the BBB) and pharmacokinetics of biopharmaceutics in different compartments of CNS.
7. Identification of relevant translational readouts which are better amenable to elucidate the role of the BBB in the pathogenesis of neurodegeneration and could eventually lead to new targets for the treatment of the neurovascular causes of the diseases.

Campo scientifico

Parole chiave

Programma(i)

Argomento(i)

Invito a presentare proposte

H2020-JTI-IMI2-2017-12-two-stage

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Meccanismo di finanziamento

RIA - Research and Innovation action

Coordinatore

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Contribution nette de l'UE
€ 2 218 291,27
Indirizzo
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
Regno Unito

Mostra sulla mappa
Regione
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 2 233 291,27

Partecipanti (27)

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Ultimo aggiornamento: 4 Novembre 2024

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Permalink: https://cordis.europa.eu/project/id/807015/it

European Union, 2024